Despite considerable progress in the development of laboratory techniques in molecular biology, the genetic epidemiology of hypertension remains undefined. As a complex polygenic disorder, hypertension presents many difficult challenges for etiologic research. The phenotype is difficult to characterize and it is likely that etiologic heterogeneity, both in terms of environmental as well as genetic factors, is present both within and between populations. The capacity to carry out a search of the entire genome creates new opportunities for this field, and in combination with continued study of known candidate genes, substantial progress could be possible over the next several years. This application is based on a large-scale on-going study of populations of African origin - the International Collaborative Study on Hypertension in Blacks. Beginning in 1991, population based surveys were initiated in 9 sites in 7 countries, including West Africa (Nigeria, Cameroon), the Caribbean (Barbados, St. Lucia and Jamaica) and the US (Maywood, IL). When completed a total 12,000 individuals will have been enrolled in the study. In the study proposed in this application we will use available registries to identify African-American participants ages 25-40 in Maywood. IL whose blood pressures are in the top quartile of the distribution. These individuals, along with available siblings and parents, will be invited for a comprehensive screening examination to characterize the hypertension.related phenotypic characteristics and to provide a DNA sample. A total sample of 250 sibships, plus parents when possible, will be enrolled. These families will provide the basis for linkage analysis and other studies 85 proposed by the network. We will also make available to the network DNA samples on 3700 individuals from the US, African and Caribbean sites in ICSHIB, including population based case-control studies of hypertensives and normotensives. These samples would make it possible to identify African-origin variants at the loci of interest, and to test the generalizability of new findings in case-control studies. An initial focus for the study of candidate genes will include the renin-angiotensin system (RAS). Laboratory assays will be performed of renin, angiotensin- converting enzyme and angiotensinogen, along with genotyping. An existing relationship with the University of Utah will be utilized to accomplish genotyping for these candidate loci in an efficient manner.